Abstract Hyperglycemia over extended periods in type 2 diabetes (T2D) leads to the accumulation of advanced glycation endproducts (AGEs) that are known to impair bone quality and cause bone fragility. T2D is associated with a higher risk of bone fractures despite increases in bone mineral density (BMD) but conventional diagnostic tools like FRAX consistently underestimate the risk of fracture in T2D patients. Glycated hemoglobin (HbA1c) has been the standard marker for dysglycemia or poor glucose control. More importantly, due to its association with glycation and with T2D, HbA1c has the potential to serve as a potent surrogate marker of bone quality and fracture risk, and add to the predictive capacity of tools like FRAX. In particular, because poor glycemic control over extended periods leads to impairment of bone quality, we propose that longitudinal assessment of HbA1c in patients with T2D should be a substantial and reliable indicator of bone health and fracture risk. With access to OptumLab?sTM administrative claims and clinical databases, containing records for more than 150 million patients, in this retrospective observational study, we seek to understand, how elevated levels of HbA1c over 2-5 years affect bone fracture incidences, while controlling for various confounding factors (Aim 1). Additionally, it is unknown whether a combination of anti-diabetic medication and anti-osteoporosis medications help in reduction of fracture risk in patients with varying levels of glycemic control. Here we will evaluate the most effective drug combinations that reduce risk of fracture in T2D patients (Aim 2). Successful completion of these two aims will provide a new understanding of the temporal effect of HbA1c levels on bone quality and fracture and will lead to substantial advancement of current diagnostic tools like FRAX for T2D populations. Furthermore, identification of specific combinations of anti-diabetic and anti-osteoporosis medications that can reduce fracture incidences in T2D populations will add to cost-effectiveness, improved quality of life and reduced mortality. !